Targeting Interleukin-10 Restores Graft Microvascular Supply and Airway Epithelium in Rejecting Allografts.
Targeting Interleukin-10 Restores Graft Microvascular Supply and Airway Epithelium in Rejecting Allografts.
复制标题
DOI：
10.3390/ijms23031269
复制
发表时间：
2022-01-23
影响因子：
5.6
通讯作者：
Broering DC
中科院分区：
文献类型：
--
作者：
Kazmi S;Khan MA;Shamma T;Altuhami A;Ahmed HA;Mohammed Assiri A;Broering DC
白细胞介素-10（IL-10）是一种重要的调节性细胞因子，在同种异体免疫炎症过程中对维持免疫耐受起着重要作用。我们以前的研究强调，IL-10介导的免疫抑制建立免疫耐受阶段，从而调节微血管和上皮的完整性，这影响炎症相关的移植功能障碍和上皮下纤维化排斥同种异体移植。在此，我们进一步研究了IL-10在小鼠气道移植模型中对微血管和上皮的修复作用。为了研究IL-10介导的微血管和上皮修复，我们耗尽和重建IL-10，并监测移植物微血管、气道上皮和相关修复蛋白。我们的数据表明，未处理的对照同种异体移植物和IL-10（−）同种异体移植物均显示出早期（d 6）微血管渗漏、组织氧合、血液灌注和裸露气道上皮的显著增加，这与移植后d10血管内皮细胞上粘附蛋白Fascin-1和β-catenin的丢失有关。然而，IL-10（+）促进早期微血管和气道上皮修复，并在移植后第10天促进内皮Fascin-1和β-catenin的成比例增加。此外，在移植后第10天，与IL-10（-）和未治疗对照相比，气道上皮细胞在同系移植物和IL-10（+）同种异体移植物中也表达显著更高的FOXJ 1和β-连环蛋白表达。总的来说，这些发现表明IL-10介导的微血管和上皮变化分别与气道上皮和血管内皮细胞上的FOXJ 1、β-连环蛋白和Fascin-1蛋白的表达相关。这些发现确立了IL-10相关微血管和上皮修复的潜在修复性调节，这可以提供重要的治疗策略以促进临床环境中的移植物修复。
Interleukin-10 (IL-10) is a vital regulatory cytokine, which plays a constructive role in maintaining immune tolerance during an alloimmune inflammation. Our previous study highlighted that IL-10 mediated immunosuppression established the immune tolerance phase and thereby modulated both microvascular and epithelial integrity, which affected inflammation-associated graft malfunctioning and sub-epithelial fibrosis in rejecting allografts. Here, we further investigated the reparative effects of IL-10 on microvasculature and epithelium in a mouse model of airway transplantation. To investigate the IL-10 mediated microvascular and epithelial repair, we depleted and reconstituted IL-10, and monitored graft microvasculature, airway epithelium, and associated repair proteins. Our data demonstrated that both untreated control allografts and IL-10 (−) allografts showed a significant early (d6) increase in microvascular leakiness, drop-in tissue oxygenation, blood perfusion, and denuded airway epithelium, which is associated with loss of adhesion protein Fascin-1 and β-catenin on vascular endothelial cells at d10 post-transplantation. However, IL-10 (+) promotes early microvascular and airway epithelial repair, and a proportional increase in endothelial Fascin-1, and β-catenin at d10 post-transplantation. Moreover, airway epithelial cells also express a significantly higher expression of FOXJ1 and β-catenin in syngrafts and IL-10 (+) allografts as compared to IL-10 (−) and untreated controls at d10 post-transplantation. Collectively, these findings demonstrated that IL-10 mediated microvascular and epithelial changes are associated with the expression of FOXJ1, β-catenin, and Fascin-1 proteins on the airway epithelial and vascular endothelial cells, respectively. These findings establish a potential reparative modulation of IL-10 associated microvascular and epithelial repair, which could provide a vital therapeutic strategy to facilitate graft repair in clinical settings.
登录
查看更多内容
影响因子：
4.6
作者：
Goto Y;Lamichhane A;Kamioka M;Sato S;Honda K;Kunisawa J;Kiyono H
通讯作者：
Kiyono H
DOI：
10.1165/rcmb.2005-0277oc
发表时间：
2006-03-01
影响因子：
6.4
作者：
Douglas, IS;del Valle, FD;Voelkel, NF
通讯作者：
Voelkel, NF
影响因子：
2.8
作者：
Cataldo, D;Munaut, C;Louis, R
通讯作者：
Louis, R
影响因子：
10
作者：
Heijink, Irene H.;de Bruin, Harold G.;Postma, Dirkje S.
通讯作者：
Postma, Dirkje S.
影响因子：
6.2
作者：
Heim, Christian;Khan, Mohammad Afzal;Ensminger, Stephan M.
通讯作者：
Ensminger, Stephan M.